Boosting the immune response Flashcards by Beth T

Triggered by IL12
Release IL2 and IFN-gamma
> Help CD8 cells to increase cell-mediated response against intracellular bacteria / protozoa
> Stimulate macrophages to form granulomas in IL12-IFNgamma network
Over-activation = Type 4 hypersensitivity

Th1 cells

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Release IL4
> Activate B cells (class switching)
> (Help with extracellular infections - Helminths)
Over-activation = Type 1 hypersensitivity (IgE production via B cells)

Th2 cells

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3 mechanisms in B cell activation by Th2 cells

CD40-CD40L
TCR-MHC class II
IL4

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Different types of CD4 cells

Th1, Th2, Treg, Th17

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> Maintain tolerance to self-antigen to prevent AI disease
(Respond to TGF-beta)
Release Foxp3

Treg

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> Neutrophil recruitment
(Respond to IL6, TGF-beta)
(Release IL17, IL21, IL22)

Th17

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Key IL released by CD4+ (Th2) for B cell activation

IL4

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Key IL released by CD4+ (Th1) for CD8+ activation

IL2

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What is the mechanism of immune memory?

APCs (incl. B cells) present antigen to CD4+ cells
Activation of B cells (via CD40 / IL4 / TCR) and CD8+ cells
Memory B cells / CD4+ / CD8+ cells form against antigen
These cells more accessible to produce faster + stronger immune response on secondary exposure to antigen

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Central vs effector memory T cells

Central: T cells migrate efficently to LNs in response to antigen exposure - produce lots of IL2 but no IFN-gamma or perforin

Effector: T cells sit in organs waiting for exposure - produce lots of IFN-gamma and perforin but little IL2

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Live (attenuated) vaccines

MMR (V) BOY

MMR, Varicella, BCG, Oral (Typhoid, Polio Sabin), Yellow fever

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Types of inactivated vaccine

Inactive organisms
Component / sub-unit
Conjugate
Toxoid

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What are the two types of Polio vaccine?

Polio Sabin (oral)
Polio Salk (non-oral)
(Neither are given now, as polio has been successfully eradicated and giving would provoke more resistance than protection)

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Polio Sabin

Oral

Live attenuated

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Polio Salk

Non-oral

Inactivated

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Mantoux test

Tuberculin bacteria purified protein derivative injected intradermally
Vaccinated / previously infected mount immune response

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HA inhibition assay

Tests for influenza vaccination
Virus added to blood
Ab to HA prevents highly condensed sticking
Diffuse spot if Ab present / condensed spot if absent

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What provides long-term immunity in:

a) TB vaccination
b) Influenza vaccination

a) T cells (‘T’B) (Type IV hypersensitivity)

b) Antibodies (Type II hypersensitivity)

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Process of immune memory in vaccination

APCs present antigen to CD4+ cells - activate B

Inactive organisms

Hepatitis A
Cholera
Polio Salk
Influenza
Rabies
Pertussis

Component

Influenza - HG, NA
HepB - HbS antigen
HPV - capsid

Conjugate

(Encapsulated bacteria):
Hib
Pneumococcus

Toxoid

Tetanus

Diphtheria

Cholera
Rabies
Hepatitis A
Pertussis

Inactivated organism

‘CRAP’

Influenza (HG, NA) HepB (HbS) HPV (capsid)

Component

Pneumococcus | Hib

Conjugate

Novel vaccine Plasmid containing gene of choice inserted into muscle - protein presented on cell surface - mimics virally infected cell to stimulate CD8+ Danger of integration into host DNA Currently on trial for West Nile Virus

DNA vaccine

Acquired defect in DC function = malignancy | May be able to mount immune response against malignancy

Dendritic cell vaccine

What are the 4 ways to boost the immune response?

1. Vaccination 2. Replace missing components 3. Block immune checkpoints 4. Cytokine therapy

What is an adjuvant?

Increases immune response without altering specificity (creates 'general inflammatory environment') Mimic PAMPs on TLR and other PRR

Freund's adjuvant

BCG

Alum adjuvant

Provokes IL4 release to activate B cells

ISCOM adjuvant

Immune stimulating complexes - saponins, cholesterol, protein

CpG adjuvant

Cytosine and guanine separated by phosphate | Stimulate TLR9

What are the main types of adjuvant?

Freund's Alum CpG ISCOM

What missing components can be replaced?

HSC transplant IVIG T cells

Permanent cure for life threatening ID (e.g. SCID, adhesion defect)

HSC transplant

Non-specific or specific (e.g. IgG to VZV) Specific used for post-exposure prophylaxis Non-specific used for primary antibody deficiency (e.g. hyper IgM), or secondary (haem malignancies, post BM transplant)

Antibody replacement

T cell replacement: a) T cells removed, stimulated by tumour cell antigens + re-infused b) T cells removed, specific TCR gene inserted into T cell DNA + re-infused c) T cells removed, stimulated by specific antigen (EBV) + re-infused d) T cells removed, specific gene to express receptors against targets on tumour cells)

a) Tumour infiltrating T cells b) TCR T cells c) Virus-specific T cells d) CAR T cells

Advanced melanoma treatments

Immune checkpoint blockers: - Anti-CTLA4 - Anti-PD1

Anti-CTLA4 as advanced melanoma treatment

Ipilimumab Immune checkpoint blocker (same CTLA4 system as abatacept - CTLA4 inhibits / CD28 stimulates T cells; CD80 and CD86 bind respectively - ipilimumab blocks CTLA4)

Anti-PD1 as advanced melanoma treatment

Pembrolizumab, Nivolumab Immune checkpoint blocker PD-1 inhibits T cells

-umab

Blocks immune checkpoint | CTLA4 or PD1

CGD treatment

IFN-gamma

Behcet's, relapsing MS treatment

IFN-beta

Hepatitis, Kaposi's, hairy cell leukaemia, CML, MM treatment

IFN-alpha